The virtues of vitamin D--but how much is too much?

Vitamin D deficiency is common in healthy adults and children as well as in the chronic kidney disease (CKD) population. What was once a disease of malnourished children in the developing world has re-emerged and reached pandemic proportions. In parallel with this development, there is a growing awareness that vitamin D is not simply a 'calcaemic hormone' but plays an important role in the prevention of cardiovascular disease, infectious and auto-immune conditions, renoprotection, glycaemic control and prevention of some common cancers. Most tissues in the body have a vitamin D receptor and the enzymatic machinery to convert 'nutritional' 25-hydroxyvitamin D to the active form 1,25-dihydroxyvitamin D; it is estimated that 3% of the human genome is regulated by the vitamin D endocrine system. Although there are few well-conducted studies on the benefits of vitamin D therapy, an exuberant use of vitamin D is now seen in the general population and at all stages of CKD. There is emerging evidence that vitamin D may in fact have a therapeutic window, and at least from the effects on the cardiovascular system, more is not necessarily better. In this review, we discuss the role of nutritional vitamin D (ergocalciferol or cholecalciferol) supplementation in CKD patients, interpreting the clinical studies in the light of the vitamin D metabolic pathway and its pluripotent effects. While nutritional vitamin D compounds clearly have numerous beneficial effects, randomised controlled studies are required to determine the effectiveness and optimal dose at different stages of CKD, its concurrent use with activated vitamin D compounds and its safety profile.